1. Field of the Invention
The present invention relates to a system and method for determining the presence or concentration of analytes biological agents in a sample of bodily fluid, such as whole blood.
2. State of the Art
Currently membranes manufactured from various polymers, such as nylon, polysulfones, polyethyersulphones and polypropylene, are used in diagnostic applications to hold dry reagents, separate blood or create an absorbent pad to hold a sample. These membranes are made using various proprietary and patented techniques and each has specific properties useful to the diagnostic test for which they are used.
The market place for diagnostic systems is increasingly important and the ability to separate blood into relatively clear fluid and red blood cells is a critical factor in many tests. The tests are hindered by the fact that the membranes currently used become translucent when blood is applied and even when the red blood cells have been separated from the relatively clear fluid components, a shadow of the red blood cells is perceived by the spectrophotometric device-used to read the test. At least two systems have attempted to compensate for the interference of red blood cells with the test reading. These systems include the Boehringer Mannheim "Accu-Chek Easy" and the LifeScan "SureStep" product. (See U.S. Design Pat. No. 367,109.) These test devices use multiple layers to separate and/or mask the interference of the red blood cells on the spectrophotometric reading taken by the test device reader. The types of materials used to separate red blood cells are fleece, glass fibers, absorbent pads and tight meshes of nylon, polypropylene or other polymers.
U.S. Pat. No. 4,340,479 describes a method for manufacturing a hydrophilic polyamide membrane. This membrane is used in U.S. Pat. No. 5,049,487 for a blood based test product which holds the reagents in a dry state prior to testing and provides a means of absorbing the blood sample during the test.
U.S. Pat. No. 5,186,843, Baumgardner et al., describes a cellulose and glass fiber material suitable for blood separation purposes.
U.S. Pat. No. 4,629,563, Wrasidlo, and U.S. Pat. No. 4,774,039, Wrasidlo, describe methods for manufacturing an asymmetric membrane which could be used to separate whole blood into relatively clear fluid and red blood cells. This type of material is referenced in U.S. Pat. No. 4,994,238, Daffern et al., and U.S. Pat. No. 4,774,192, Terminiello et al., to separate whole blood into relatively clear fluid and red blood cells.
U.S. Pat. No. 4,994,238, Daffem et al., teaches a device which uses an asymmetrically porous membrane having progressively finer filtration with increasing distance from the dosing surface. This patent further teaches an asymmetric membrane that provides a determined saturation volume and that provides progressively finer filtration which acts to filter cellular components of the sample at or near the sample receiving surface.
U.S. Pat. No. 4,774,192, Terminiello et al., teaches, for method of preparing a dry chemistry reagent system for detection and analysis of heterogeneous fluid samples. This patent also provides for a specific porous membrane of essentially uniform composition and a porosity gradient that extends from one surface to the opposite surface
U.S. Pat. No. 5,456,835, Castino et al., teaches removing hemoglobin from blood by using a filter and hollow fiber or flat sheet of polyethersulfone. This system is used to filter out the leukocytes, hemoglobin and debris from blood.
U.S. Pat. Nos. 5,306,623 and 5,418,142, Kiser et al., teach a porous matrix with separation coating uniformly impregnated within. U.S. Pat. No. 5,418,142 more specifically defines the pore size. These patents teach that, as whole blood moves through the membrane, red blood cells encounter the separation component embedded in the matrix, whereby clear fluid passes through to the test side.
An object of the present invention is to improve the properties of transverse flow-through membranes for enzyme/substrate color development systems.
Another object of this invention is to provide a method for increasing the filtration performance of the membrane.
Yet another object of the invention is to provide a method to impregnate the membrane with fillers to block the interference of the red blood cells with the diagnostic reaction and the reading of the test indication.
Still another object of the invention is to provide an improved method for manufacturing test devices.